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Prorenin receptor is essential for podocyte autophagy and survival

Item Type:Article
Title:Prorenin receptor is essential for podocyte autophagy and survival
Creators Name:Riediger, F. and Quack, I. and Qadri, F. and Hartleben, B. and Park, J.K. and Potthoff, S.A. and Sohn, D. and Sihn, G. and Rousselle, A. and Fokuhl, V. and Maschke, U. and Purfürst, B. and Schneider, W. and Rump, L.C. and Luft, F.C. and Dechend, R. and Bader, M. and Huber, T.B. and Nguyen, G. and Mueller, D.N.
Abstract:The prorenin receptor (PRR) is highly expressed in podocytes, but its role in the maintenance of podocyte function is unknown. Here we generated podocyte-specific PRR-knockout mice and found that these animals died between 2 to 3 wk after birth. Within 14 d, PRR-knockout mice developed nephrotic syndrome, albuminuria with podocyte foot-process fusion, and cytoskeletal changes. Podocyte-specific PRR deletion also led to disturbed processing of multivesicular bodies and enrichment of autophagosomal (LC3) and lysosomal (LAMP2) markers, indicating a functional block in autophagosome-lysosome fusion and an overload of the proteasomal protein-degradation machinery. In vitro, PRR knockdown and pharmacologic blockade of vacuolar H(+)-ATPases, which associate with the PRR, increased vesicular pH, led to accumulation of LC3-positive and LAMP2-positive vesicles and altered the cytoskeleton. Taken together, these results suggest that the PRR is essential for podocyte function and survival by maintaining autophagy and protein-turnover machinery. Furthermore, PRR contributes to the control of lysosomal pH, which is important for podocyte survival and cytoskeletal integrity.
Keywords:Autophagy, Cell Survival, Podocytes, Cell Surface Receptors, Animals, Mice
Source:Journal of the American Society of Nephrology
Publisher:American Society of Nephrology
Page Range:2193-2202
Date:December 2011
Official Publication:https://doi.org/10.1681/ASN.2011020200
PubMed:View item in PubMed

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